Targeting of drugs to the colon through oral administration of drugs is attractive and important for two reasons: 1) large bowel diseases, such as ulcerative colitis or Crohn's Disease, can be treated locally, thus avoiding enema dosage forms and minimizing systemic absorption; and 2) drugs that may be absorbed in the colon but which are degraded in the upper digestive tract (e.g., protein and peptide drugs), can be made available orally, since the colonic site minimizes the exposure of these compounds to the multitude of degradative digestive and proteolytic enzymes present in the upper digestive tract. Even though it would be expected that the absorption of most drugs from the colon is slower than from the small intestine, this is balanced by the longer residence time (17-72 hours) in the colon (1).
Dew et al. (2) reported that the application of a Eudragit S based coating (which is widely used to produce acid resistant formulations) is reasonably effective in the release of drug in the ascending colon. The concept of enteric coating to deliver drugs to the colon is thus proposed. However, Eudragit S dissolves above pH 7. If the pH of the upper intestinal tract reaches 7, then this Eudragit S coating will dissolve and the dosage form will release drug prior to reaching the colon. Saffran et al. (3) reported the use of azo polymers for colonic delivery. These polymers are degraded by colonic bacterial azo-reductase activity, but are unaffected by acid conditions or action of gastrointestinal enzymes, and therefore could be used as potential coatings for colonic delivery. However, these coatings depend on the presence of colonic anaerobic bacteria for their optimum performance. Also, the safety of these polymers is not well established.
A system based on a time-controlled explosion mechanism is described in U.S. Pat. No. 4,871,549 in which drug release is caused by explosion of a membrane after a definite time period (4). The system was described for various types of controlled release applications. The formulations only had a semipermeable membrane coating, thus the system would start operating once the dosage form was in contact with gastrointestinal fluid, irrespective of whether the fluid was gastric or intestinal.
A delivery system for targeting the colon is described in U.S. Pat. No. 5,171,580. This delivery system consists of an enteric outer coating, a high viscosity grade of hydrophilic polymer layer which can swell when exposed to the intestinal fluid, and an anionic copolymer inner layer, EUDRAGIT S, which is soluble at a pH above 7.0, surrounding a core containing the active ingredient. Due to a small quantity of liquid in the colon, therefore, the use of high viscosity grade of polymer could diminish the drug availability to be absorbed if the dosage form reached to the colon prior to complete dissolution of the polymer. Moreover, the swelling nature of the high viscosity grade of polymer could cause cracking of the enteric coating, resulting in failure of the delivery system, if even a small amount of gastric fluid penetrated the enteric coating during the time that the delivery system stays in the stomach.